Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death
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2021
Authors
Krunić, MatijaRistić, Biljana
Bošnjak, Mihajlo
Paunović, Verica
Tovilović-Kovačević, Gordana
Zagović, Nevena
Mirčić, Aleksandar
Marković, Zoran
Todorović Marković, Biljana
Jovanović, Svetlana
Kleut, Duška
Mojović, Miloš
Nakarada, Đura
Marković, Olivera S.
Vuković, Irena
Harhaji-Trajković, Ljubica
Trajković, Vladimir
Article (Published version)
Metadata
Show full item recordAbstract
We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent
apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers
displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of
GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (
•
OH), superoxide
anion (O2
•− ), and lipid peroxidation. Nonselective antioxidants, •
OH scavenging, and iron chelators, but not
superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •
OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for o...ptimal
protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective
effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The
antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and
dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early
(wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of
GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •
OH/NO
scavenging and induction of cytoprotective autophagy.
Keywords:
Graphene quantum dots / Sodium nitroprusside / Neurotoxicity / Oxidative stress / Hydroxyl radical / Nitric oxide / AutophagySource:
Free Radical Biology and Medicine, 2021, 177, 167-180Publisher:
- Elsevier
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200110 (University of Belgrade, Faculty of Medicine) (RS-MESTD-inst-2020-200110)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200017 (University of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča) (RS-MESTD-inst-2020-200017)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-MESTD-inst-2020-200026)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200146 (University of Belgrade, Faculty of Physical Chemistry) (RS-MESTD-inst-2020-200146)
DOI: 10.1016/j.freeradbiomed.2021.10.025
ISSN: 0891-5849
WoS: 000717740300004
Scopus: 2-s2.0-85117824181
Collections
Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Krunić, Matija AU - Ristić, Biljana AU - Bošnjak, Mihajlo AU - Paunović, Verica AU - Tovilović-Kovačević, Gordana AU - Zagović, Nevena AU - Mirčić, Aleksandar AU - Marković, Zoran AU - Todorović Marković, Biljana AU - Jovanović, Svetlana AU - Kleut, Duška AU - Mojović, Miloš AU - Nakarada, Đura AU - Marković, Olivera S. AU - Vuković, Irena AU - Harhaji-Trajković, Ljubica AU - Trajković, Vladimir PY - 2021 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5467 AB - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical ( • OH), superoxide anion (O2 •− ), and lipid peroxidation. Nonselective antioxidants, • OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing • OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both • OH/NO scavenging and induction of cytoprotective autophagy. PB - Elsevier T2 - Free Radical Biology and Medicine T1 - Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death VL - 177 SP - 167 EP - 180 DO - 10.1016/j.freeradbiomed.2021.10.025 ER -
@article{ author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zagović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera S. and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir", year = "2021", abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical ( • OH), superoxide anion (O2 •− ), and lipid peroxidation. Nonselective antioxidants, • OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing • OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both • OH/NO scavenging and induction of cytoprotective autophagy.", publisher = "Elsevier", journal = "Free Radical Biology and Medicine", title = "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death", volume = "177", pages = "167-180", doi = "10.1016/j.freeradbiomed.2021.10.025" }
Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zagović, N., Mirčić, A., Marković, Z., Todorović Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O. S., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine Elsevier., 177, 167-180. https://doi.org/10.1016/j.freeradbiomed.2021.10.025
Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zagović N, Mirčić A, Marković Z, Todorović Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković OS, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180. doi:10.1016/j.freeradbiomed.2021.10.025 .
Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zagović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera S., Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180, https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .